Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion

Balázs Démuth, Attila Farkas, Attila Balogh, Karolina Bartosiewicz, Barnabás Kállai-Szabó, Johny Bertels, Tamás Vigh, Jurgen Mensch, Geert Verreck, Ivo Van Assche, G. Marosi, Zsombor K. Nagy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation is in a quite early phase. Development of high speed electrospinning opened up the possibility to study tableting of electrospun solid dispersions (containing polyvinylpyrrolidone-vinyl acetate and itraconazole [ITR] in this case). This work was conducted to investigate the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting. The dissolution rates from tablets proved to be mainly composition dependent. Magnesium stearate acted as a nucleation promoting agent (providing an active hydrophobic environment for crystallization of ITR) hindering the total dissolution of ITR. This crystallization process proved to be temperature dependent as well. However, the extent of dissolution of more than 95% was realizable when a less hydrophobic lubricant, sodium stearyl fumarate (soluble in the medium), was applied. Magnesium stearate induced crystallization even if it was put in the dissolution medium next to proper tablets. After optimization of the composition, scaled-up tableting on a rotary press was carried out. Appropriate dissolution of ITR from tablets was maintained for 3 months at 25°C/60% relative humidity. HPLC measurements confirmed that ITR was chemically stable both in the course of downstream processing and storage.

Original languageEnglish
Pages (from-to)2982-2988
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume105
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Lubricants
Itraconazole
Crystallization
Tablets
Povidone
Excipients
Humidity
High Pressure Liquid Chromatography
Temperature

Keywords

  • amorphous
  • chemical stability
  • crystallization
  • dissolution
  • nanotechnology
  • oral drug delivery
  • Raman spectroscopy
  • solid dispersion
  • tableting

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Démuth, B., Farkas, A., Balogh, A., Bartosiewicz, K., Kállai-Szabó, B., Bertels, J., ... Nagy, Z. K. (2016). Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion. Journal of Pharmaceutical Sciences, 105(9), 2982-2988. https://doi.org/10.1016/j.xphs.2016.04.032

Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion. / Démuth, Balázs; Farkas, Attila; Balogh, Attila; Bartosiewicz, Karolina; Kállai-Szabó, Barnabás; Bertels, Johny; Vigh, Tamás; Mensch, Jurgen; Verreck, Geert; Van Assche, Ivo; Marosi, G.; Nagy, Zsombor K.

In: Journal of Pharmaceutical Sciences, Vol. 105, No. 9, 01.09.2016, p. 2982-2988.

Research output: Contribution to journalArticle

Démuth, B, Farkas, A, Balogh, A, Bartosiewicz, K, Kállai-Szabó, B, Bertels, J, Vigh, T, Mensch, J, Verreck, G, Van Assche, I, Marosi, G & Nagy, ZK 2016, 'Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion', Journal of Pharmaceutical Sciences, vol. 105, no. 9, pp. 2982-2988. https://doi.org/10.1016/j.xphs.2016.04.032
Démuth, Balázs ; Farkas, Attila ; Balogh, Attila ; Bartosiewicz, Karolina ; Kállai-Szabó, Barnabás ; Bertels, Johny ; Vigh, Tamás ; Mensch, Jurgen ; Verreck, Geert ; Van Assche, Ivo ; Marosi, G. ; Nagy, Zsombor K. / Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion. In: Journal of Pharmaceutical Sciences. 2016 ; Vol. 105, No. 9. pp. 2982-2988.
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